Functionally Selective AT(1) Receptor Activation Reduces Ischemia Reperfusion Injury

TY - JOUR

T1 - Functionally Selective AT(1) Receptor Activation Reduces Ischemia Reperfusion Injury

AU - Hostrup, Anders

AU - Christensen, Gitte Lund

AU - Bentzen, Bo Hjort

AU - Liang, Bo

AU - Aplin, Mark

AU - Grunnet, Morten

AU - Hansen, Jakob Lerche

AU - Jespersen, Thomas

N1 - Copyright © 2012 S. Karger AG, Basel.

PY - 2012/8

Y1 - 2012/8

N2 - Angiotensin II (AngII) is a key peptide in cardiovascular homeostasis and is a ligand for the Angiotensin II type 1 and 2 seven transmembrane receptors (AT 1 R and AT 2 R). The AT 1 receptor is a seven-transmembrane (7TM) G protein-coupled receptor (GPCR) mediating the majority of the physiological functions of AngII. The AT 1 R mediates its effects through both G protein-dependent and independent signaling, which can be separated by functionally selective agonists. In the present study we investigate the effect of AngII and the β-arrestin biased agonist [SII]AngII on ischemia-reperfusion injury in rat hearts. Isolated hearts mounted in a Langendorff perfused rat heart preparations showed that preconditioning with [SII]AngII reduced the infarct size induced by global ischemia from 46±8.4% to 22±3.4%. In contrast, neither preconditioning with AngII nor postconditioning with AngII or [SII]AngII had a protective effect. Together these results demonstrate a cardioprotective effect of simultaneous blockade of G protein signaling and activation of G protein independent signaling through AT 1 receptors.

AB - Angiotensin II (AngII) is a key peptide in cardiovascular homeostasis and is a ligand for the Angiotensin II type 1 and 2 seven transmembrane receptors (AT 1 R and AT 2 R). The AT 1 receptor is a seven-transmembrane (7TM) G protein-coupled receptor (GPCR) mediating the majority of the physiological functions of AngII. The AT 1 R mediates its effects through both G protein-dependent and independent signaling, which can be separated by functionally selective agonists. In the present study we investigate the effect of AngII and the β-arrestin biased agonist [SII]AngII on ischemia-reperfusion injury in rat hearts. Isolated hearts mounted in a Langendorff perfused rat heart preparations showed that preconditioning with [SII]AngII reduced the infarct size induced by global ischemia from 46±8.4% to 22±3.4%. In contrast, neither preconditioning with AngII nor postconditioning with AngII or [SII]AngII had a protective effect. Together these results demonstrate a cardioprotective effect of simultaneous blockade of G protein signaling and activation of G protein independent signaling through AT 1 receptors.

U2 - 10.1159/000341445

DO - 10.1159/000341445

M3 - Journal article

C2 - 22854413

SN - 1015-8987

VL - 30

SP - 642

EP - 652

JO - Cellular Physiology and Biochemistry

JF - Cellular Physiology and Biochemistry

IS - 3

ER -